{"paper_id":"1f6a5e32-6d24-4147-9715-beabd9a3f01c","body_text":"CLINICAL INVESTIGATION NON-VASCULAR INTERVENTIONS\nEthanol Sclerotherapy in the Management of Ovarian\nEndometrioma: Technical Considerations for Catheter-\nand Needle-Directed Sclerotherapy\nAynur Azizova 1 • Turkmen Turan Ciftci 1 • Murat Gultekin 2 • Emre Unal 1 •\nOkan Akhan 1 • Gurkan Bozdag 2 • Devrim Akinci 1\nReceived: 15 September 2023 / Accepted: 22 February 2024 / Published online: 29 March 2024\n/C211 The Author(s) 2024\nAbstract\nPurpose To provide technical guidance on applying\ncatheter-directed and needle-directed ethanol sclerotherapy\nfor endometriomas and present the results of these scle-\nrotherapy methods.\nMaterials and Methods From January 2015 to March\n2021, the results of the patients with symptomatic ovarian\nendometriomas who underwent needle-directed or catheter-\ndirected sclerotherapy were evaluated, retrospectively. The\ndecision to apply which sclerotherapy technique was made\nduring the procedure for each patient considering the fol-\nlowing factors: cyst size, cyst location, cyst viscosity, and\ntissue rigidity.\nResults Both needle-directed ( n = 34 cysts) and catheter-\ndirected ( n = 34 cysts) sclerotherapy techniques were\neffective, with a 100% technical success rate and a 97%\nclinical success rate. In two of 34 cysts (6%) treated with\nneedle-directed sclerotherapy, recurrence was detected and\nsuccessfully retreated with catheter-directed sclerotherapy.\nSigniﬁcant reductions in cyst size, pain, and serum cancer\nantigen 125 levels ( p \\ 0.05) were noted. Serum anti-\nMu¨llerian hormone levels remained unaffected, indicating\npreserved ovarian reserve ( p [ 0.05). Among those treated\nfor infertility, the pregnancy rate was 54% ( n = 6/11). The\nmean ± SD cyst size decline was greater in catheter-di-\nrected sclerotherapy than needle-directed sclerotherapy\n(5.5 ± 3.1 cm vs. 4.0 ± 2.1 cm, p \\ 0.05). However, the\npretreatment cyst volumes were considerably higher in\ncatheter-directed sclerotherapy group (202.0 ± 233.5 mL\nvs. 78.8 ± 59.7 mL, p \\ 0.05) and were associated with\nsigniﬁcant post-treatment volume decrease ( p \\ 0.05).\nConclusion The choice between catheter-directed and\nneedle-directed ethanol sclerotherapy should be deter-\nmined during the procedure, with a preference for catheter-\ndirected sclerotherapy when feasible. Crucial factors in\nmaking this decision include cyst size, cyst location, cyst\nviscosity, and tissue rigidity.\nLevel of evidence Level 3, non-controlled retrospective\ncohort study.\n& Okan Akhan\nakhano@tr.net\nAynur Azizova\ndr.aynur.azizova@gmail.com\nTurkmen Turan Ciftci\nturkmenciftci@yahoo.com\nMurat Gultekin\nmrtgultekin@yahoo.com\nEmre Unal\nemreunal.rad@gmail.com\nGurkan Bozdag\ngbozdag@hacettepe.edu.tr\nDevrim Akinci\nakincid@hotmail.com\n1 Department of Radiology, Hacettepe University School of\nMedicine, 06100 Sihhiye, Ankara, Turkey\n2 Department of Obstetrics and Gynecology, Hacettepe\nUniversity School of Medicine, 06100 Sihhiye, Ankara,\nTurkey\n123\nCardiovasc Intervent Radiol (2024) 47:891–900\nhttps://doi.org/10.1007/s00270-024-03694-0\n\n\nGraphical Abstract\nKeywords Endometriosis /C1Infertility /C1\nDysmenorrhea /C1Ethanol sclerotherapy /C1Ovarian\nreserve /C1AMH\nIntroduction\nEndometriosis is an estrogen-dependent chronic benign\ndisease occurring due to the endometrial tissue existence in\nthe extrauterine environment and affecting approximately\n10% of women of reproductive age [1]. Endometrioma is the\nmost common form of pelvic endometriosis, characterized\nby a cystic lesion with the wall consisting of endometrial\nmucosa occurring following recurrent hemorrhages. Patients\nwith endometriosis frequently complain of dysmenorrhea,\nchronic pelvic pain, or dyspareunia. Additionally,\nendometriosis is associated with diminished ovarian reserve\nand infertility. The reported endometriosis frequency in\ninfertile women is approximately 25–50% [ 1–5].\nOvarian endometrioma treatment aims to treat life\nquality reducing symptoms, such as dysmenorrhea, and\npreserve ovarian reserve by minimizing ovarian injury.\nAlthough surgical excision is the standard treatment\nmethod, the depreciation in ovarian reserve owing to\nremoving healthy ovarian tissue adjacent to endometrioma\nor electrocoagulation is inevitable. Although oral contra-\nceptives are used for the treatment, their utilization is\nlimited due to high recurrence rates and side effects such as\nthromboembolism [ 4–7].\nEthanol sclerotherapy applied to treat benign cystic\nlesions of solid organs has also been used to treat\nendometrioma, primarily due to its minimally invasive\nfeature. It has been shown that ethanol sclerotherapy pre-\nserves ovarian reserve due to the precise targeting\nendometrioma without causing normal ovarian tissue\ndamage. Moreover, a marked decrease in the cyst size\ndissolves the mass effect on the ovary and is associated\nwith better ovarian reserve [ 4, 5]. A recent meta-analysis\nassessing the effectiveness of ultrasound-guided scle-\nrotherapy for endometrioma concluded that it is a safe and\nefﬁcient method for managing recurrence, infertility, and\npain [ 8].\nEthanol sclerotherapy can be performed via a needle [ 9]\nor a catheter [ 4]. Some drawbacks of needle-directed\nsclerotherapy (NDS) compared to catheter-directed scle-\nrotherapy (CDS) include difﬁculties in effectively evacu-\nating viscous endometrioma content with a 16–18-gauge\nneedle, potential needle dislodgement, leading to leakage\nof cyst contents and peritoneal adhesions, and decreased\ntreatment efﬁcacy. NDS for multiloculated lesions is also\ntechnically challenging, resulting in inadequate cyst con-\ntent evacuation and reduced treatment efﬁcacy. Moreover,\nrecurrence rates after NDS range from 0 to 62% in the\nliterature. [ 4]. However, the technical considerations for\nEthanol Sclerotherapy in the Management of Ovarian Endometrioma: Technical \nConsiderations for Catheter- and Needle-Directed Sclerotherapy\nIf the proper technique is applied, both catheter- and needle-directed sclerotherapy are effective methods in endometrioma treatment\nRule out malignancy using subtracted contrast-enhanced T1-weighted images before proceeding with ethanol sclerotherapy\nTechnical pitfalls for treatment technique\nPrefer CDS over NDS if it is feasible\nThe choice between CDS and NDS \nshould be determined during the \nprocedure\n• Small cyst size (3-4 cm) > prefer NDS\n Cyst location- >1 cm from the anterior \nabdominal wall and vaginal wall > \nprefer NDS \n High tissue rigidity recognized during \nthe needle puncture > prefer NDS\n High cyst viscosity that can not even be \ndiluted via irrigation > prefer CDS \nCDS\nNDS\nPretreatment (a,b,d,e) and posttreatment (c,f) MR images\n123\n892 A. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma …\n\npatient selection in choosing between CDS or NDS remain\nunclear.\nThis study aimed to provide interventional radiologists\nwith technical guidance on applying ethanol sclerotherapy\nfor endometriomas by elucidating when to perform the\nprocedure through a catheter or a needle based on our\nsingle-center experience and presenting the results of these\nsclerotherapy methods.\nMaterials and Methods\nThis retrospective observational descriptive study was\napproved by the institutional review board and designed\nfollowing the STrengthening and Reporting of OBserva-\ntional studies in Epidemiology (STROBE) guidelines.\nPicture archiving and communication systems with elec-\ntronic medical records were searched to collect patients’\ndata from January 2015 to March 2021. All patients with\novarian endometrioma treated with ethanol sclerotherapy\ndue to pain or infertility complaints were included con-\nsecutively. Patients lost to follow-up were excluded.\nAll patients were evaluated with ultrasound and con-\ntrast-enhanced magnetic resonance imaging (CE-MRI) to\nconﬁrm endometrioma diagnosis and exclude malignancy.\nObtaining subtraction images of pre-contrast T1-weighted\nimages from post-contrast T1-weighted images was\nmandatory to rule out malignancy. Complaints such as pain\nand infertility were questioned, and Visual Analogue Scale\n(VAS) scores were recorded. Serum cancer antigen 125\n(CA-125) and serum anti-Mu ¨llerian hormone (AMH)\nlevels were measured.\nThe treatment decision was taken after evaluation of the\npatient in the multidisciplinary team forum involving at\nleast one interventional radiologist and a gynecologist. The\npreferred primary treatment method for ovarian\nendometrioma was ethanol sclerotherapy, aiming to pre-\nserve ovarian reserve. Inclusion criteria for sclerotherapy\nwere (i) cysts concordant with endometrioma, (ii) cysts\nwithout the sign of malignancy such as a solid enhancing\ncomponent according to CE-MRI, (iii) maximum cyst\ndiameter larger than 3 cm, (iv) symptomatic cysts associ-\nated with pain or infertility, (v) the presence of the access\nto the cyst via the transabdominal or transvaginal route.\nExclusion criteria for sclerotherapy were (i) cysts with the\nsign of malignancy and (ii) the absence of the transab-\ndominal access and inability to use the transvaginal route\ndue to virginity. Surgery was considered only for these\nexcluded cases.\nAll patients were treated as inpatients after obtaining\ninformed consent. Coagulation parameters (platelet\ncount [ 50,000/lL and international normalized ratio \\\n1.2) were determined. All procedures were performed by\none of three interventional radiologists (E.U., T.T.C., D.A.)\nwho had at least ﬁve years of experience. Procedures were\nperformed in an interventional radiology unit equipped\nwith ﬂuoroscopy and ultrasound in the supine or lithotomy\nposition under sterile conditions. Intravenous sedation was\nadministered by the anesthesiologist using midazolam\n(0.05–0.1 mg/kg), fentanyl (0.5–1 lg/kg), and propofol\n(0.5–1 mg/kg).\nTreatment Techniques: Selection Criteria\nThe choice between CDS or NDS technique was determined\nduring the procedure for each patient, taking into account the\nfollowing factors collectively: (i) cyst size—small cysts with\nmaximum diameter between 3 and 4 cm were treated with\nNDS as catheter placement in small cysts increase the risk of\nrupture; CDS was preferred for the cysts [ 4 cm, (ii) cyst\nlocation—cysts located more than 1 cm away from the\nanterior abdominal or vaginal wall, with intraabdominal\ntissues like bowel loops or paraovarian vascular structures in\nbetween, were treated with NDS; otherwise, CDS was the\npreferred approach, (iii) cyst viscosity—if the viscosity of\nendometrioma content was high that cannot even be diluted\nvia irrigation, CDS was preferred over NDS, (iv) tissue\nrigidity—if the rigidity of tissues, especially vaginal wall,\nrecognized during the needle puncture was high, the tech-\nnique of choice was NDS as catheter placement could\nincrease the rupture risk. Treatments were performed using\ntransabdominal or transvaginal access. Cysts with the pos-\nsibility of direct access from the anterior abdominal wall\nwere treated via transabdominal route, and otherwise,\ntransvaginal access was preferred. All multiloculated cysts\nwere treated with CDS. Patients with multiple cysts were\ntreated in the same session.\nNeedle-Directed Sclerotherapy Technique\nThe cyst was punctured using an 18-gauge Chiba needle\nunder sonographic guidance (Fig. 1a). Approximately 20%\nof the estimated cyst volume was aspirated; subsequently,\nthe contrast agent (Ultravist 300/100 mg/mL; Bayer, Lev-\nerkusen, Germany), less than the aspirated content, was\ninjected under ﬂuoroscopic guidance to conﬁrm the leak-\nage absence (Fig. 1b). After that, irrigation with 3–5 mL\nsterile saline injections and aspirations was performed to\nreduce the viscosity of the hemorrhagic cyst content\n(Fig. 1c). When the cyst content became completely ser-\nous, the remaining content was aspirated almost entirely by\nkeeping the tip of the needle within the cavity. Eventually,\nsclerotherapy was performed with sterile 96% ethanol\n(50% of the estimated volume, not to exceed 100 mL) for\n15 min (Fig. 1d). Finally, the procedure was terminated\nafter the reaspiration of the ethanol.\n123\nA. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma … 893\n\nCatheter-Directed Sclerotherapy Technique\nAfter puncturing the cyst with an 18-gauge needle\n(Fig. 2a), a 0.035-inch Amplatz guidewire (Boston Scien-\ntiﬁc, USA) was advanced into the cyst under ultrasound\nand ﬂuoroscopy guidance through the needle (Fig. 2b). In\nthe presence of the multilocular cyst, the internal septa\nwere mechanically fragmented with a 0.035-inch guidewire\nand dilator manipulation. Next, an 8-F drainage catheter\n(Skater, Argon Medical Devices, USA) was placed\n(Fig. 2c). After the cyst content evacuation and obtaining a\ncystogram to conﬁrm the leakage absence, sclerotherapy\nwas performed with sterile 96% ethanol for 15 min. The\ncatheter was withdrawn after the evacuation of the entire\nethanol content, and the procedure was terminated (Sup-\nplementary Video 1).\nFig. 1 NDS technique. a Under\ntransvaginal ultrasound\nguidance, right ovarian\nendometrioma was punctured\nusing an 18-gauge Chiba needle.\nb After aspiration of roughly\n20% of the estimated cyst\nvolume, the contrast agent less\nthan the aspirated content was\ninjected under ﬂuoroscopic\nguidance to verify the absence\nof leakage. c Next, the viscosity\nof the cyst content was reduced\nby irrigation with sterile saline\ninjections and aspirations.\nd After the cyst content turned\nserous, sclerotherapy was\napplied with sterile 96% ethanol\nfor 15 min. The procedure was\nterminated after the reaspiration\nof the ethanol. NDS = needle-\ndirected sclerotherapy\nFig. 2 CDS technique. a Under transabdominal ultrasound guidance,\nthe left ovarian endometrioma was punctured with an 18-gauge\nneedle. b Then, a 0.035-inch Amplatz guidewire was advanced into\nthe cyst under ultrasound and ﬂuoroscopy guidance through the\nneedle, and c an 8-F drainage catheter was placed. After the\nevacuation of the cyst content and obtaining a cystogram to verify the\nabsence of leakage, sclerotherapy was applied with sterile 96%\nethanol for 15 min. Finally, the procedure was terminated after the\nreaspiration of the ethanol. CDS = catheter-directed sclerotherapy\n123\n894 A. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma …\n\nPost-Procedural Care\nThe aspirated cyst content was sent for cytological exam-\nination. All patients were monitored in the recovery area\nfor 1 h and transferred to inpatient hospitalization. They\nwere discharged after 4–6 h of follow-up or the following\nday if they had normal vital signs. Complications related to\nthe procedure were recorded. Patients were followed up\nwith ultrasound and/or MRI 3 and 6 months after the\nprocedure and annually, thereafter. In addition, VAS\nscores, serum CA-125, and AMH levels were evaluated\nduring each follow-up.\nDeﬁnitions and Statistical Analysis\nTechnical success was deﬁned as accomplishing all pro-\ncedure steps without any intraprocedural complication.\nClinical success was deﬁned as the reduction or disap-\npearance of cysts, decline (VAS score to 1–3 range), or\ndisappearance (VAS = 0) of pain in follow-up. Clinical\nfailure was deﬁned as an increase or no decrease in cyst\nsize and complaints. An increase in cyst size was consid-\nered as recurrence. The cyst volumes were calculated using\nthe ellipsoid formula (largest three axes 9 0.523) on\nultrasound and MRI. The serum CA-125 and serum AMH\nlevels before the treatment and at the last follow-up were\nevaluated. Complications were deﬁned using the Cardio-\nvascular and Interventional Radiological Society of Europe\n(CIRSE) classiﬁcation for complications [ 10]. The degree\nof pain before and after the treatment was determined from\n0 to 10 points using VAS [ 11, 12].\nAll statistical analyses were conducted using SPSS 11.5\n(IBM) software. Quantitative variables were described\nusing mean ± standard deviation or median (minimum–\nmaximum), while qualitative variables were described\nusing the number of patients/cysts (percentage). Student’s\nt-test or Mann–Whitney U test was used to compare\nquantitative variables between two categories of qualitative\nvariables, depending on normal distribution assumptions.\nFor qualitative variables with more than two categories,\none-way ANOVA or Kruskal–Wallis H test was applied\nbased on normal distribution assumptions. Chi-square and\nFisher-exact tests examined the relationship between two\nqualitative variables. Differences between two quantitative\ndependent variables were assessed using the paired t-test or\nWilcoxon sign test, depending on normal distribution\nassumptions. A p-value of \\ 0.05 was considered statisti-\ncally signiﬁcant.\nTable 1 Baseline characteristics of patients and cysts\nCharacteristics Values\nAge (year)\nMean ? SD 30.0 ± 5.8\nMedian (Min–Max.) 30.0 (15.0–40.0)\nCysts per patient\nMean ? SD 1.3 ± 0.6\nMedian (Min–Max.) 1.0 (1.0–4.0)\nLocation of cysts, n(%)\nUnilateral 39.0 (76.0)\nBilateral 12.0 (24.0)\nMorphology of cysts, n(%)\nUnilocular 61.0 (90.0)\nMultilocular 7.0 (10.0)\nMain symptom, n(%)\nPain 40.0 (78.0)\nInfertility 11.0 (22.0)\nOral contraceptive use before treatment, n(%)\nYes 3.0 (6.0)\nNo 48.0 (94.0)\nHistory of surgery for endometrioma before treatment, n(%)\nYes 1.0 (2.0)\nNo 50.0 (98.0)\nTreatment technique, n(%)\nCDS 34.0 (50.0)\nNDS 34.0 (50.0)\nTreatment route, n(%)\nTransabdominal 39.0 (57.0)\nTransvaginal 29.0 (43.0)\nTreatment-related complication, n(%)\nYes 1.0 (2.0)\nNo 50.0 (98.0)\nHospitalization days\nMean ? SD 0.7 ± 0.4\nMedian (Min.–Max.) 1.0 (0.0–1.0)\nFollow-up periods (months)\nMean ? SD 14.5 ± 11.0\nMedian (Min.-Max.) 14.0 (1.0–55.0)\nPain relief in patients who treated for pain, n(%)\nYes 40.0 (100.0)\nNo 0.0 (0.0)\nPost-treatment pregnancy who treated for infertility, n(%)\nYes 6.0 (54.0)\nNo 5.0 (46.0)\nSD Standard deviation, Min Minimum, Max Maximum, CDS\nCatheter-directed sclerotherapy, NDS Needle-directed sclerotherapy\n123\nA. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma … 895\n\nResults\nFifty-one consecutive patients (main complaint: pain\nn = 40, infertility n = 11) with 68 cysts treated with ethanol\nsclerotherapy were included in this study. Four patients with\nfour cysts were excluded due to loss to follow-up. Table 1\nsummarizes the baseline characteristics of participants.\nThe technical success rate was 100%. CDS and NDS were\nused to treat 34 (50%) and 34 (50%) cysts, respectively. All\naspirates were conﬁrmed to contain hemosiderin-laden\nmacrophages compatible with endometrioma and were\nnegative for malignancy. The mean ± SD length of hospital\nstay was 0.7 ± 0.4 days. The mean ± SD follow-up was\n14.5 ± 11.0 months (range: 1.0–55.0 months). The only\ncomplication (grade 3 [10]) was cavity infection observed in\none patient (2%) treated with NDS via vaginal approach.\nFifteen days after the procedure, the patient was admitted to\nthe emergency department with a high fever, raising suspi-\ncion of cavity infection. A sample was taken from the treated\nresidual cyst cavity via vaginal needle aspiration, showing a\nnegative culture for infection. Considering no other cause\nfor the fever, it was attributed to a procedure-related com-\nplication and treated with intravenous antibiotics, leading to\nresolution and subsequent discharge of the patient.\nThe clinical success rate was 97%. The recurrence rate\nwas 3%. One patient with two cysts, initially treated with\nNDS for infertility, necessitated retreatment due to recur-\nrence, with cyst volumes increasing by 70% nine months\npost-procedure. Following the second session with CDS,\nthere was a remarkable 98% reduction in cyst volumes nine\nmonths after the subsequent procedure.\nThere was a signiﬁcant reduction in cyst size, pain, and\nserum CA-125 levels ( p \\ 0.001). All patients treated for\npain experienced pain relief ( n = 40, p \\ 0.001), with\ncomplete pain resolution (VAS = 0) in 75% ( n = 30) and a\nsigniﬁcant decrease in pain (VAS = 1–3) in 25% ( n = 10).\nSerum AMH levels showed no signiﬁcant difference\nbetween pretreatment and last follow-up values (p = 0.822).\nOverall, pregnancy was observed in eight patients, six of\nwhom were treated for infertility, resulting in a pregnancy\nrate of 54% ( n = 6/11; spontaneous n = 5, in vitro fertil-\nization n = 1). The pretreatment and post-treatment images\nof two patients are shown in Fig. 3. Table 2, Figs. 4, and 5\nsummarize the outcomes of ethanol sclerotherapy.\nFurthermore, clinical success rates were compared\nbetween CDS and NDS, with 50% of cysts treated with\neach technique (CDS: n = 34, NDS: n = 34). The decrease\nin maximum cyst diameter ( p = 0.021) and cyst volume\n(p = 0.016) was more signiﬁcant in the CDS group than in\nthe NDS group (Table 3). The pretreatment cyst volumes\nwere larger in those treated with CDS than NDS\n(p = 0.033) (Fig. 6), and the large pretreatment cyst vol-\nume was associated with a signiﬁcant post-treatment size\ndecrease (\np \\ 0.001). The cysts disappeared at the last\nfollow-up with a rate of 53% ( n = 18) in the CDS group\nand 50% ( n = 17) in the NDS group, indicating no\nFig. 3 The pretreatment and posttreatment images of two different\npatients treated with ethanol sclerotherapy. a, b, c A 27-year-old\npatient with right ovarian endometrioma complaining of pain was\ntreated with CDS. In the 54-months follow-up, the huge cyst\n(transverse T1W( a)/T2W(b) images, red arrows) disappeared (c-\ntransverse T2W image, red arrow). d, e, f A 37-year-old patient with\nleft ovarian endometrioma was treated for infertility with NDS. In the\n16-months follow-up, the cyst (transverse T1W( d)/T2W(e) images,\nblue arrows) regressed almost completely (transverse T2W( f) image,\nblue arrow)\n123\n896 A. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma …\n\nsigniﬁcant difference between these techniques\n(p = 1.000). There was no difference between these two\ngroups in terms of other variables; see Table 3.\nThe selection of participants for the study and results of\nthe study are summarized as ﬂowchart in Fig. 7.\nDiscussion\nThis retrospective study provides key factors that should be\nconsidered in the decision-making process of choosing\nCDS or NDS, including cyst size, cyst location, cyst\nTable 2 Outcomes of ethanol sclerotherapy\nVariables Before treatment After treatment p value\nMean ± SD Median (Min–Max.) Mean ± SD Median (Min–Max.)\nMaximum diameter of cysts (cm) 6.5 ± 2.4 6.0 (3.2–14.0) 1.8 ± 2.1 0.6 (0.0–7.8) < 0.001 a\nVolume of cysts (mL) 140.4 ± 179.8 81.0 (11.0–856.0) 12.0 ± 22.9 0.0 (0.0–119.0) < 0.001 a\nVAS score 8.8 ± 2.4 10.0 (0.0–10.0) 0.5 ± 0.9 0.0 (0.0–3.0) < 0.001 a\nSerum AMH level (ng/l) 2.3 ± 1.9 1.94 (0.0–7.2) 2.4 ± 2.3 1.7 (0.0–8.0) 0.822 a\nSerum CA-125 level (U/ml) 121.7 ± 217.6 63.30 (4.7–1306.7) 43.1 ± 39.1 30.1 (5.2–182.3) < 0.001 a\nStatistically signiﬁcant values are highlighted in bold within the ‘ ‘ p value’ ’ column\na Wilcoxon sign test, SD Standard deviation, Min Minimum, Max Maximum, VAS Visual analogue scale, AMH Anti-Mullerian hormone, CA-\n125 Cancer antigen 125\nFig. 4 Graph showing changes\nin all variables after ethanol\nsclerotherapy. The timepoint of\npost-treatment indicates the last\nfollow-up, a duration that varied\namong all study subjects. Note a\nsigniﬁcant decrease in all\nvariables, excluding serum\nAMH level, which did not\nreduce and was associated with\npreserved ovarian reserve after\nethanol sclerotherapy treatment.\nVAS = Visual Analogue Scale,\nAMH = anti-Mu¨llerian\nhormone, CA-125 = cancer\nantigen 125\nFig. 5 Graph showing changes\nof cyst volume according to\nfollow-up times. Note the\ndecrease in cyst volumes as the\nfollow-up time increases\n123\nA. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma … 897\n\nviscosity, and tissue rigidity, based on our single-center\nexperience. Since cyst viscosity and tissue rigidity are\nunpredictable before the procedure, the decision on CDS or\nNDS was made during the procedure. Half of the cysts\nwere treated with CDS and another half with NDS. There\nwere signiﬁcant reductions in maximum cyst size, pain,\nand serum CA-125 levels in all patients ( p \\ 0.001), with\nno decrease in serum AMH levels ( p = 0.822). CDS\nshowed a greater reduction in cyst sizes compared to NDS\n(p \\ 0.05). Pretreatment cyst sizes were larger in the CDS\ngroup ( p = 0.033), correlating with a more pronounced\npost-treatment size decrease ( p \\ 0.001), suggesting that\nthe larger pretreatment cyst size in the CDS group may\ncontribute to the greater reduction in cyst sizes.\nIn this study, both treatment techniques were associated\nwith high clinical success. One patient with two cysts initially\ntreated with NDS experienced recurrence, which was suc-\ncessfully treated with CDS in the second session. In the study\nof Noma and Yoshida [ 13], recurrence rates were 62.5%,\n9.1%, and 3.8% in groups treated with ethanol instilled\nfor \\ 10 min, [ 10 min, and laparoscopic cystectomy,\nrespectively, indicating signiﬁcant differences in recurrence\nrates based on the timing of ethanol sclerotherapy. In our\nstudy, the timing for sclerotherapy was consistently set at\n15 min. Additionally, in contrast to our approach, they did not\napply irrigation during NDS, possibly leading to higher\nrecurrence rates compared to surgical intervention.\nTable 3 Comparison of CDS and NDS techniques\nDifferences in variables before treatment and at last\nfollow-up after treatment\nTreatment technique\nCDS NDS p value\nMean ± SD Median (Min–\nMax.)\nMean ± SD Median (Min–Max.)\nDifference in the maximum diameters of cysts (cm) 5.5 ± 3.1 5.0 (0.2–14.0) 4.0 ± 2.1 3.5 (0.9–8.7) 0.021a\nDifference in the volumes of cysts (mL) 191.5 ± 227.0 91.6 (10.0–856.0) 65.3 ± 51.4 54.0 (11.0–218.0) 0.016b\nDifference in the VAS scores 7.5 ± 3.2 8.0 (0.0–10.0) 9.2 ± 1.0 9.5 (7.0–10.0) 0.163 b\nDifference in the serum AMH levels (ng/l) 0.4 ± 1.5 0.1 ( - 2.4–5.3) -0.1 ± 0.9 - 0.3 ( - 2.3–2.6) 0.224 b\nDifference in the serum CA-125 levels (U/ml) 48.7 ± 64.9 32.7\n(- 18.0–305.7)\n107.2 ± 285.2 15.7\n(- 104.8–1294.6)\n0.522b\nStatistically signiﬁcant values are highlighted in bold within the ‘ ‘ p value’ ’ column\nCDS Catheter-directed sclerotherapy, NDS Needle-directed sclerotherapy, a Student-t test, b Mann–Whitney U test, SD Standard deviation,\nMin Minimum, Max Maximum, VAS Visual analogue scale, AMH Anti-Mullerian hormone, CA-125 Cancer antigen 125\nFig. 6 Graph showing changes of cyst volume according to the\ntreatment technique. The decrease in the cyst volume is more\nsigniﬁcant in CDS group than in the NDS group. The pretreatment\ncyst sizes are larger in those treated with CDS than NDS, and it was\nshown that the large pretreatment cyst size is associated with a\nsigniﬁcant post-treatment size decrease. Furthermore, there is no\nsigniﬁcant difference between these techniques according to ﬁnal cyst\nvolume. CDS = catheter-directed sclerotherapy, NDS = needle-di-\nrected sclerotherapy\n123\n898 A. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma …\n\nEthanol sclerotherapy offers a critical advantage in pre-\nserving ovarian reserve compared to surgery, which inevi-\ntably leads to a decrease in ovarian tissue due to adjacent\ntissue removal or electrocoagulation [5, 14–23]. Roman et al.\n[22] demonstrated signiﬁcant ovarian tissue removal during\nsurgery, proportionate to cyst size. However, in sclerother-\napy, solely endometrioma is targeted; that is why normal\novarian tissue is not damaged, and serum AMH levels do not\ndecrease [4, 24–27]. Vaduva et al. [ 28] compared NDS with\nlaparoscopic cystectomy, showing a signiﬁcant decrease in\nAMH levels in the latter group. Nevertheless, a recent meta-\nanalysis [29] found no statistically signiﬁcant differences in\nrecurrence and pregnancy rates between surgery and scle-\nrotherapy groups, although this review included various\nsclerosing agents such as tetracycline besides ethanol. In our\nstudy, all sessions utilized 95% sterile ethanol sclerotherapy,\nchosen over surgery unless malignancy was suspected, with\nthe ﬁnal decision made during a multidisciplinary forum\ninvolving gynecologists and interventional radiologists.\nThe main limitation of this study was its retrospective\ndesign. Furthermore, we did not compare ethanol scle-\nrotherapy with other treatment techniques, including sur-\ngery with or without hormonal therapy. Therefore, further\nstudies are needed to compare both CDS and NDS with\nsurgical techniques. Other signiﬁcant limitations were a\nrelatively short follow-up period (14.5 months) and a small\nsample size (51 patients, 68 cysts).\nIn conclusion, both catheter- and needle-directed etha-\nnol sclerotherapy are effective methods preserving ovarian\nreserve in endometrioma treatment if the proper technique\nis applied. The choice between CDS and NDS should be\ndetermined during the procedure, with a preference for\nCDS when feasible. Crucial factors in making this decision\ninclude cyst size, cyst location, viscosity of cyst content,\nand tissue rigidity. It is essential to rule out malignancy\nusing subtracted contrast-enhanced T1-weighted images\nbefore proceeding with ethanol sclerotherapy.\nSupplementary Information The online version contains\nsupplementary material available at https://doi.org/10.1007/s00270-\n024-03694-0.\nAcknowledgements Not available\nFunding Open access funding provided by the Scientiﬁc and Tech-\nnological Research Council of Tu ¨rkiye (TU¨ BI˙TAK). This research\ndid not receive any speciﬁc grant from funding agencies in the public,\ncommercial, or not-for-proﬁt sectors.\nDeclarations\nConﬂict of interest The author declare that they have no conﬂict of\ninterest.\nEthical Approval This retrospective observational descriptive study\nwas approved by the institutional review board of Hacettepe\nUniversity (decision number 2021/10-13).\nFig. 7 Flowchart summarizing the selection of participants for the\nstudy, and results of the study. VAS = Visual Analogue Scale,\nAMH = anti-Mu¨llerian hormone, CA-125 = cancer antigen 125,\nCDS = catheter-directed sclerotherapy, NDS = needle-directed scle-\nrotherapy, IVF = in vitro fertilization\n123\nA. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma … 899\n\nOpen Access This article is licensed under a Creative Commons\nAttribution 4.0 International License, which permits use, sharing,\nadaptation, distribution and reproduction in any medium or format, as\nlong as you give appropriate credit to the original author(s) and the\nsource, provide a link to the Creative Commons licence, and indicate\nif changes were made. The images or other third party material in this\narticle are included in the article’s Creative Commons licence, unless\nindicated otherwise in a credit line to the material. If material is not\nincluded in the article’s Creative Commons licence and your intended\nuse is not permitted by statutory regulation or exceeds the permitted\nuse, you will need to obtain permission directly from the copyright\nholder. To view a copy of this licence, visit http://creativecommons.\norg/licenses/by/4.0/.\nReferences\n1. Bulun SE. Endometriosis. N Engl J Med. 2009;360:268–79.\n2. Bulletti C, Coccia ME, Battistoni S, Borini A. Endometriosis and\ninfertility. J Assist Reprod Genet. 2010;27:441–7.\n3. Kwok H, Jiang H, Li T, Yang H, Fei H, Cheng L, et al. Lesion\ndistribution characteristics of deep inﬁltrating endometriosis with\novarian endometrioma: an observational clinical study. BMC\nWomens Health. 2020;20:111.\n4. Han K, Seo SK, Kim M-D, Kim GM, Kwon JH, Kim HJ, et al.\nCatheter-directed sclerotherapy for ovarian endometrioma: short-\nterm outcomes. Radiology. 2018;289:854–9.\n5. Cohen A, Almog B, Tulandi T. 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Medicina. 2023. https://doi.org/10.3390/\nmedicina59091643.\nPublisher’s Note Springer Nature remains neutral with regard to\njurisdictional claims in published maps and institutional afﬁliations.\n123\n900 A. Azizova et al.: Ethanol Sclerotherapy in the Management of Ovarian Endometrioma …","source_license":"CC0","license_restricted":false}